NM_001365631.1:c.3881A>G

Variant names:

• chr3-33517081-T-C
• rs183373873
• NM_001365631.1:c.3881A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001365631.1(CLASP2):​c.3881A>G​(p.Tyr1294Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000291 in 1,613,734 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (3 hom.)
• Consequence: CLASP2 NM_001365631.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.57
• Publications: 2 publications found

Genes affected

CLASP2 (HGNC:17078): (cytoplasmic linker associated protein 2) Enables cytoskeletal protein binding activity; dystroglycan binding activity; and protein tyrosine kinase binding activity. Involved in several processes, including microtubule cytoskeleton organization; positive regulation of extracellular matrix organization; and regulation of supramolecular fiber organization. Located in several cellular components, including basal cortex; cortical microtubule plus-end; and ruffle membrane. Colocalizes with focal adhesion; kinetochore; and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0079548955).
• BP6: Variant 3-33517081-T-C is Benign according to our data. Variant chr3-33517081-T-C is described in ClinVar as Benign. ClinVar VariationId is 3041004.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 43 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365631.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP2	NM_001365631.1	MANE Select	c.3881A>G	p.Tyr1294Cys	missense	Exon 35 of 39	NP_001352560.1	A0A804HJG7
	CLASP2	NM_001365628.1		c.3968A>G	p.Tyr1323Cys	missense	Exon 36 of 40	NP_001352557.1
	CLASP2	NM_001365629.1		c.3965A>G	p.Tyr1322Cys	missense	Exon 36 of 40	NP_001352558.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLASP2	ENST00000682230.1	MANE Select	c.3881A>G	p.Tyr1294Cys	missense	Exon 35 of 39	ENSP00000507498.1	A0A804HJG7
	CLASP2	ENST00000468888.6	TSL:5	c.3905A>G	p.Tyr1302Cys	missense	Exon 35 of 39	ENSP00000419974.2	E7EW49
	CLASP2	ENST00000399362.8	TSL:5	c.3902A>G	p.Tyr1301Cys	missense	Exon 35 of 39	ENSP00000382297.4	E7ERI8

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000695 AC: 173 AN: 249074 AF XY: 0.000622

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00940

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000291 AC: 426 AN: 1461408 Hom.: 3 Cov.: 31 AF XY: 0.000270 AC XY: 196 AN XY: 726996

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.0103 AC: 407 AN: 39624

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111752

Other (OTH) AF: 0.000182 AC: 11 AN: 60360

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152326 Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26 AN XY: 74494

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00771 AC: 40 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000273 Hom.: 0

Bravo AF: 0.000348

ExAC AF: 0.000786 AC: 95

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CLASP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.27
Sift	Benign	0.21	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.23
MVP		0.56
MPC		0.57
ClinPred		0.048	T
GERP RS		3.2
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs183373873; hg19: chr3-33558573; COSMIC: COSV56278503;